The major objective of our studies is to inquire into the role of CMI in recurrent genital HSV-2 infections. The working hypothesis argues that recurrences are related to a defect in CMI response, particularly in the generation of effector cells from memory cells. This insufficiency in effector functions allows virus replication and pathogenesis to proceed unimpeded until sufficient effector cells are generated to control viral pathogenesis. In order to test these various possibilities, the experimental design consists in the study of temporal CMI responses to HSV-2 antigen in patients experiencing recurrent genital infections. In order to determine the nature of the defect, we propose to study various HSV-2 antigens, including AG-e, a viral protein(s) located in the envelope and expressed in cervical tumor cells and cervical cells productively infected with the virus. Also, we propose to use CMI assays designed to define immune memory (lymphocyte transformation), and effector functions (LIF and MAF production and lymphocyte mediated cytotoxicity). The mechanism of the proposed defect in memory to effector cell conversion will be studied.